Gene therapy restored memory in mice with Alzheimer's disease
Alzheimer's disease is the main cause of the development of senile dementia. To date, there are no effective methods of treating this disease, which is partly due to a lack of information about cellular mechanisms that lead to impaired transmission of information along nerve fibers and memory impairment in the early stages of the disease.
Researchers at the Independent University of Barcelona, working under the guidance of Dr. Carlos Saura, identified the cellular mechanism involved in memory formation and developed a gene therapy approach that restores memory impairment in mouse models of early-stage Alzheimer's disease.
In search of a target gene, the researchers compared gene expression profiles in hippocampal cells of healthy control mice and transgenic mice with early-stage Alzheimer's disease. Using DNA microarrays, they identified genes (transcriptome) and proteins (proteome) expressed in each mouse at different stages of the disease. As a result of the subsequent comparison, they found that the complex of genes involved in memory formation coincides with the complex of genes regulating the functions of the Crtc1 protein (CREB-regulated transcription coactivator-1). This protein, in turn, regulates the work of genes associated with glucose metabolism and cancer development. Disruption of the functions of this group of genes leads to memory disorders in the early stages of Alzheimer's disease.
In patients with this disease, the formation of aggregates of abnormally altered beta-amyloid protein in brain tissue interferes with the normal functioning of Crtc1. This, according to Dr. Saur, prevents the activation of genes responsible for the functioning of synapses, which negatively affects the processes of memorization.
The method of gene therapy developed by the authors consists in the introduction into the hippocampus of the mouse brain of a viral vector containing a gene that provides the production of Crtc1 protein. The result of such therapy is the restoration of signals necessary for the activation of genes that ensure the formation of long-term memory.
The results obtained may form the basis of a new therapeutic approach to the treatment of Alzheimer's disease. The authors hope that in the future specialists will be able to develop pharmacological preparations for activating the Crtc1 protein in order to prevent, slow down or restore cognitive function disorders in patients with Alzheimer's disease.
Article by Parra-Damas et al. Crtc1 Activates a Transcriptional Program Derived at Early Alzheimer's Disease-Related Stages published in the Journal of Neuroscience.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Universitat Autonoma de Barcelona:
Loss of Memory in Alzheimer's Mice Models Reversed through Gene Therapy.
25.04.2014